Page 377 - Textbook of Pathology, 6th Edition

cannot be readily treated and do not respond to erythro- of 2 or 3 cell lineage and monocytosis but no blasts; marrow 361
poietin, androgens. Splenectomy may be necessary in some shows <5% blasts.
cases. In general, chronic idiopathic myelofibrosis has poorer 4. RCMD with ringed sideroblasts (RCMD-RS): New entity.
outcome compared with PV and ET. Incidence 15%; all blood and marrow findings similar to
RCMD plus in addition >15% ringed sideroblasts in marrow.
MYELODYSPLASTIC SYNDROMES 5. Refractory anaemia with excess blasts (RAEB-1): RAEB
of FAB category 3 divided into 2 subtypes with combined
Definition and Classification
incidence of 40%. RAEB –1 has blood cytopenia with <5%
Myelodysplastic syndromes (MDS) are a heterogeneous blasts and monocytosis; marrow blast count 5-9%.
group of haematopoietic clonal stem cell disorders having 6. RAEB-2: Findings of blood and marrow similar to
abnormal development of different marrow elements (i.e. RAEB-1 but marrow blast count is 10-19%.
dysmyelopoiesis), usually characterised by cytopenias, 7. Myelodysplastic syndrome unclassified (MDS-U): New
associated with cellular marrow and ineffective blood cell entity in MDS. Blood cytopenia without any blasts; marrow
formation. These conditions are, therefore, also termed as shows dysplasia of myeloid and thrombocytic cell lineage
preleukaemic syndromes or dysmyelopoietic syndromes. and marrow blast count <5%.
There have been two main classification schemes for CHAPTER 14
MDS: 8. MDS with isolated del (5q): New entity in MDS. Anaemia
in blood and blasts <5%; marrow blasts <5%, normal or
FAB CLASSIFICATION OF MDS (1983): FAB (French- increased megakaryocytes and characteristic isolated
American-British) Cooperative Group classified MDS into deletion of 5q.
the following 5 groups:
1. Refractory anaemia (RA). Pathophysiology
2. Refractory anaemia with ringed sideroblasts (primary Primary MDS is idiopathic but factors implicated in etiology
acquired sideroblastic anaemia) (RARS). are radiation exposure and benzene carcinogen. Secondary
3. Refractory anaemia with excess blasts (RAEB). (therapy-related) MDS may occur following earlier anti-
4. Chronic myelomonocytic leukaemia (CMML). cancer treatment, aplastic anaemia treated with immuno-
suppressive therapy and in Fanconi’s anaemia. Several
5. Refractory anaemia with excess of blasts in cytogenetic abnormalities are seen in about 50% of MDS
transformation (RAEB-t). which include trisomy, translocations and deletions. Cases
As per FAB classification, the marrow may contain <30% evolving into leukaemia more often have aneuploidy. At
myeloblasts in MDS and this was considered as the dividing molecular level, mutations are seen in N-RAS oncogene and
line for distinguishing cases of AML (blasts >30%) from MDS. p53 anti-oncogene, which together with suppressed
WHO CLASSIFICATION OF MDS (2002): According to the immunity, accelerate apoptosis in the bone marrow.
WHO classification, patients with blast count of 20-30% and Mutations in the mitochondrial genes probably account for Disorders of Leucocytes and Lymphoreticular Tissues
labelled as RAEB-t (group 5 above) in FAB classification have occurrence of sideroblastic anaemia in MDS and conse-
prognosis similar to patients with blast count above 30% (i.e. quently disordered iron metabolism and ineffective
AML cases). Thus, as per WHO classification, marrow blast erythropoiesis.
count for making the diagnosis of AML has been revised
and brought down to 20%. Thus, patients with FAB category Clinical Features
of RAEB-t (i.e. group 5 above) are currently considered and In general, MDS is found more frequently in older people
treated as cases of AML and therefore the term RAEB-t stands past 6th decade of life, with slight male preponderance.
excluded from WHO MDS classification. Besides, the WHO Therapy-related MDS is generally not age-related and may
classification excludes CMML (FAB category 4) from MDS occur about a decade after anti-cancer therapy. Clinical
and puts in the hybrid category of myelodysplastic/ features are quite non-specific and MDS may be discovered
myeloproliferative disorder since CMML behaves like a during routine CBC examination done for some other cause.
myeloproliferative disorder; moreover refractory anaemia in At presentation the patient may have following features:
it is not due to erythroid lineage which was considered as an 1. Anaemia appreciated by pallor, fatigue and weakness.
inclusion criteria for MDS. Thus, the WHO classification of 2. Fever.
MDS consists of following 8 categories: 3. Weight loss.
1. Refractory anaemia (RA): Same as FAB type 1 MDS. 4. Sweet syndrome having neutrophilic dermatosis seen in
Incidence 5-10%; characterised by anaemia without any blasts some cases.
in blood; marrow may show <5% blasts. 5. Splenomegaly seen in 20% cases of MDS.
2. Refractory anaemia with ringed sideroblasts (RARS): Laboratory Findings
Same as FAB type 2 MDS. Incidence 10-12%; all findings in Various combinations of features are seen in different
blood and marrow similar to RA above but in addition types of MDS. In general, laboratory findings are as under:
marrow may show >15% ringed sideroblasts.
3. Refractory cytopenia with multilineage dysplasia BLOOD FINDINGS. There is cytopenia affecting two
(RCMD): New entity. Incidence 24%; blood shows cytopenia (bi-) or all the three blood cell lines (pancytopenia):